Integrin-specific activation of Rac controls progression through the G1 phase of the cell cycle Journal Article
| Authors: | Mettouchi, A.; Klein, S.; Guo, W.; Lopez-Lago, M.; Lemichez, E.; Westwick, J. K.; Giancotti, F. G. |
| Article Title: | Integrin-specific activation of Rac controls progression through the G1 phase of the cell cycle |
| Abstract: | Adhesion to fibronectin through the α5β1 integrin enables endothelial cells to proliferate in response to growth factors, whereas adhesion to laminin through α2β1 results in growth arrest under the same conditions. On laminin, endothelial cells fail to translate Cyclin D1 mRNA and activate CDK4 and CDK6. Activated Rac, but not MEK1, PI-3K, or Akt, rescues biosynthesis of cyclin D1 and progression through the G1 phase. Conversely, dominant negative Rac prevents these events on fibronectin. Mitogens promote activation of Rac on fibronectin but not laminin. This process is mediated by SOS and PI-3K and requires coordinate upstream signals through Shc and FAK. These results indicate that Rac is a crucial mediator of the integrin-specific control of cell cycle in endothelial cells. |
| Keywords: | signal transduction; epidermal growth factor; mitogen activated protein kinase; controlled study; unclassified drug; human cell; proto-oncogene proteins; cell proliferation; proteins; cells, cultured; mitogen activated protein kinase kinase 1; cell growth; map kinase signaling system; enzyme activation; phosphatidylinositol 3 kinase; endothelium cell; fibroblast growth factor 2; biosynthesis; recombinant fusion proteins; endothelium, vascular; messenger rna; protein-serine-threonine kinases; 1-phosphatidylinositol 3-kinase; immunoblotting; rna translation; adaptor proteins, signal transducing; insulin; microscopy, fluorescence; protein-tyrosine kinases; cyclin d1; mitogen-activated protein kinases; cyclin-dependent kinases; cyclin dependent kinase; growth factor; cell adhesion; blotting, northern; focal adhesion kinase; integrin; cell cycle g1 phase; g1 phase; laminin; cyclin dependent kinase 4; rac protein; integrins; cyclin-dependent kinase 4; focal adhesion protein-tyrosine kinases; growth inhibition; fibronectin; adaptor proteins, vesicular transport; mitogenic agent; cyclin dependent kinase 6; protein shc; focal adhesion kinase 1; cyclin-dependent kinase 2; cyclin-dependent kinase 6; rac gtp-binding proteins; very late activation antigen 5; fibronectins; culture media, serum-free; focal adhesions; caveolin 1; cdc2-cdc28 kinases; humans; human; article; very late activation antigen 2; receptors, fibronectin; caveolins; sos protein; receptors, collagen; sos1 protein |
| Journal Title: | Molecular Cell |
| Volume: | 8 |
| Issue: | 1 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2001-07-01 |
| Start Page: | 115 |
| End Page: | 127 |
| Language: | English |
| DOI: | 10.1016/s1097-2765(01)00285-4 |
| PUBMED: | 11511365 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work